Title: Multi-point MR-ARFI for time-efficient volumetric tissue stiffness imaging The ability to detect and characterize changes in tissue properties that are indicative of necrosis is essential for successful control of ablative therapies. As tissue is ablated, changes occur in cell structure, in the distribution of tissue water, and in the nature of the macromolecular structure. Imaging techniques that discriminate and accurately characterize tissue property changes are critically needed to ensure ablative therapy success. Focused ultrasound (FUS), a completely non-invasive and highly promising interventional technology that is able to ablate a range of pathologies, has a critical need for improved methods to detect, monitor, and interpret the resulting changes in tissue properties. MRI guidance of FUS (MRgFUS) procedures provides excellent anatomic images of tissues to be treated and normal tissues to be spared, and can monitor temperature distribution changes in aqueous (non-adipose) tissues to ensure treatment efficacy and safety. Diagnostic ultrasound, when used for guiding FUS (USgFUS) procedures, has poor anatomic image quality and limited ability to measure temperature, but can image tissue stiffness and mechanical properties that change with treatment. Although MRI can measure tissue stiffness in terms of displacement caused by an acoustic radiation force impulse (MR-ARFI), the force is typically applied at a single point, providing only a local measurement of tissue stiffness. Although MR-ARFI could sequentially interrogate multiple positions at a cost of increased acquisition time, there is not a time efficient method to simultaneously interrogate the distribution of tissue stiffness at multiple points. Our goal in this study is to develop and evaluate a time-efficient MR-ARFI method for volumetric tissue stiffness imaging. This goal will be accomplished with three aims: 1) Implement and evaluate efficiencies in interleaving multiple single-point MR-ARFI measurements; 2) Implement and evaluate simultaneous or near simultaneous multiple-point MR-ARFI methods; 3) Evaluate the accuracy and repeatability of multiple point MR-ARFI displacement measurements. This new method of volumetric stiffness imaging will enable future studies to measure tissue stiffness properties before, during, and after MRgFUS procedures, and to correlate tissue property changes with other factors such as thermal dose during the procedure and the histologic state of the tissue after the procedure. Assessing tissue displacement in response to the applied force of FUS will allow an effective remote palpation of the evolving thermal lesion formed by the MRgFUS treatment at multiple positions and times during the procedure. If this stiffness change is an indicator of necrosis, this will increase the amount of information available to determine a successful outcome.